DETAILED ACTION
Notice of Pre-AIA or AIA Status
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Continued Examination Under 37 CFR 1.114
1. A request for continued examination under 37 CFR 1.114, including the fee set forth in 37 CFR 1.17(e), was filed in this application after final rejection. Since this application is eligible for continued examination under 37 CFR 1.114, and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114. Applicant's submission filed on November 21, 2025 has been entered.
2. Claims 24, 32, 34, 41, 47 and 54 have been amended as requested in the amendment filed November 21, 2025. Following the amendment, claims 24-26, 28-32, 34-36, 38-41, 47 and 49-54 are pending in the present application.
3. Claims 24-26, 28-32, 34-36, 38-41, 47 and 49-54 are under examination in the current office action.
Withdrawn Claim Rejections
4. The rejection of claims 24-26, 28-32, 34-36, 38-41, 47 and 49-54 under 35 U.S.C. 112(a) (new matter), as set forth at section 4 of the 05/21/2025 office action, is withdrawn in view of applicant’s amendments to the claims.
5. The rejection of claims 24-26, 28-32, 34-36, 38-41, 47 and 49-54 under 35 U.S.C. 103 as being unpatentable over Lang et al. (US 2015/0366949) in view of Schulte et al. (2015), as set forth at section 5 of the 05/21/2025 office action, is withdrawn in view of applicant’s claim amendments that now recite the subject has Alzheimer’s and a gamma-secretase inhibitor/modulator is also administered in the therapeutic method.
New Claim Objections and Rejections, Necessitated by Amendment
Claim Objections
6. Claim 47 is objected to because of the following informalities: as amended, line 1 of claim 47 recites “A method of inhibiting and/or b-amyloid accumulation and/or Tau aggregation…” and appears to be missing a word or phrase after the added “and/or”. Appropriate correction is required.
Claim Rejections - 35 USC § 103
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
7. Claim(s) 24-26, 28-32, 34-36, 38-41, 47 and 49-54 is/are rejected under 35 U.S.C. 103 as being unpatentable over Lang et al. (US 2015/0366949 A1; of record) in view of Besidski et al. (US 2016/0108022 A1).
Lang et al. teach a therapeutic method of treating a disease of the nervous system that is a neurological disorder or a neural degenerative disorder, such as Alzheimer’s disease (AD) ([0013]-[0016]), wherein the method comprises administering a therapeutic agent that includes a therapeutic peptide having at least 70%, 85%, 90%, 95%, or 100% homology to SEQ ID NO: 37 ([0008], [0019], [0022]). Note that Lang’s peptide of SEQ ID NO: 37 (EHXERLKANDSLKL, wherein X is either Thr (T) or Met (M)) is identical to the sequence of instant SEQ ID NO: 16. Thus, Lang provides for a therapeutic method that is directly on point to the step of administering “(a) a therapeutic agent comprising a therapeutic peptide” as in present claims 24-25, 28, 34-35, 38, 47, 49 and 51.
Regarding claims 26, 36 and 50, Lang indicates that the peptide of SEQ ID NO: 37 can include one or more conservative substitutions ([0103]), wherein the conservative substitutions can be of amino acid residues 4E (substituted with D or Q), 5R (substituted with H, L or K), 6L (substituted with I, V or M), 7K (substituted with R or H), 9N (substituted with E or N), 12L (substituted with I, V or M), and/or 13K (substituted with R or H) ([0104]). This disclosure is identical the recited substitutions within instant claims 26, 26 and 50.
Regarding claims 29-31, 39-40 and 52-53, Lang teaches that the therapeutic peptide is linked to a transport moiety to facilitate uptake of the therapeutic peptides by the cell, wherein the transport moiety can be an HIV Tat transport moiety ([0010], [0123], [0125] and [0213]). Lang teaches that the desired cell to receive such therapy is a neuron ([0043], [0049] and [0084]-[0085]).
Finally, regarding claims 32, 41 and 54, Lang discloses that for the treatment of neurological disorders in which the growth pathways of neurons within the CNS is desired, the therapeutic peptides may be used in combination with neural growth factors, such as BDNF (brain-derived neurotrophic factor), NGF (nerve growth factor), NT-3 (neurotrophin-3), CTNF (ciliary neurotrophic factor), and GDNF (glial-derived neurotrophic factor) ([0203]).
However, while Lang teaches the therapeutic administration of the therapeutic peptide of SEQ ID NO: 37 (i.e., the instant SEQ ID NO: 16) for the treatment of a subject having AD, Lang does not teach that the method also comprises administering a g-secretase inhibitor or g-secretase modulator, as in claims 24 and 34, or that the method also comprises administering an NMDA receptor antagonist as in claim 48, or that the method further comprises administering an acetylcholinesterase inhibitor, as in claims 32, 41 and 54.
Besidski et al. teach g-secretase modulator compounds and their use in the treatment of an amyloid-b-related pathology, such as AD, which method comprises administering to a subject a therapeutically effective amount of a g-secretase modulator ([0005]-[0006], [0008] and [0040]-[0043]). According to Besidski, g-secretase cleaves at the C-terminus of amyloid precursor protein (APP), and the activity of g-secretase causes the liberation of many Ab peptides, such as Ab37, Ab38, Ab39, Ab40, Ab42 and Ab43 ([0003]-[0004]). Besidski teaches that the disclosed compounds inhibit the production of Ab40 and Ab42, while increasing Ab37 and Ab38 levels and maintaining Notch signaling ([0006] and [0008]). Thus, Besidski’s compounds inhibit the proteolysis of neuronal amyloid precursor protein (APP) as in claim 24. And because the Ab42 peptide is prone to form oligomers and fibrillar deposits (which are characteristic pathological features of AD) (see [0004]), the reduction of Ab42 peptides would necessarily inhibit and/or reduce Ab accumulation in a subject, as in claims 34 and 47.
Besidski further discloses that the treatment of Ab-related pathology using the compound of the invention may be combined with one or more conventional therapies, such as acetylcholinesterase inhibitors (donepezil, rivastigmine, galantamine, tacrine), anti-inflammatory agents, or memantine (i.e., an NMDA receptor antagonist) ([0045], [0049] and [0050](vi)). Besidski indicates that Alzheimer’s therapies specifically include donepezil, memantine, rivastigmine, galantamine and tacrine (section (vi) of [0050]).
Accordingly, it would have been obvious to one of ordinary skill in the art at the time of filing to have administered the therapeutic peptide of Lang in combination with a g-secretase modulator compound of Besidski, and one or more additional therapeutic agents according to Besidski, for the treatment of a subject having AD and thereby arrive at the presently claimed invention. MPEP § 2144.06, section I, states that “[i]t is prima facie obvious to combine two compositions each of which is taught by the prior art to be useful for the same purpose, in order to form a third composition to be used for the very same purpose.... [T]he idea of combining them flows logically from their having been individually taught in the prior art.” In re Kerkhoven, 626 F.2d 846, 850, 205 USPQ 1069, 1072 (CCPA 1980) (citations omitted). In the instant case, not only are both the therapeutic peptide of Lang and the g-secretase modulator of Besidski taught to be useful for the treatment of AD, but Besidski also explicitly teaches that the g-secretase modulator compound can be administered in combination with other AD therapies, such as acetylcholinesterase inhibitors or NMDA receptor antagonists. Similarly, Lang teaches that the therapeutic peptide can be used in conjunction with a neural growth factor, indicating its suitability for combination with other therapeutic strategies and/or agents. Therefore, the combined administration of the prior art agents for the treatment of a subject having AD would have been obvious and predictable.
8. Claim(s) 47 and 49-54 is/are rejected under 35 U.S.C. 103 as being unpatentable over Lang et al. (US 2015/0366949 A1; of record) in view of Atri (Am J Manag Care. 2011; 17:S346-S355).
The teachings of Lang et al. have been discussed above and provide for a therapeutic method for the treatment of Alzheimer’s disease (AD) in a subject comprising administering a therapeutic peptide comprising the amino acid sequence of SEQ ID NO: 37 (i.e., the instant SEQ ID NO: 16), wherein the sequence may have specific substitutions, and wherein the peptide may be linked to a transport moiety such as an HIV Tat transport moiety, which addresses claims 47(a) and 49-51. Lang also teaches that the therapeutic peptide may be used in combination with a nerve growth factor ([0203]).
However, Lang does not teach that the therapeutic peptide is administered with an NMDA receptor antagonist as in claim 47(b), or that the method may further comprise the administration of an acetylcholinesterase inhibitor, as in claim 54.
Atri teaches that there is accumulating and convergent evidence that the combined administration of cholinesterase inhibitors (ChEIs) such as donepezil, galantamine or rivastigmine and the NMDA receptor antagonist memantine in patients having mild to moderate AD reduce cognitive decline in cognition and daily function, and delay nursing home placement (see abstract). As shown in the Figure at p. S350, for example, the long-term trajectory of cognitive and functional decline in patients receiving ChEI + memantine combination therapy is significantly less severe than the worsening decline found in patients treated with ChEI monotherapy or no medication.
It would have been obvious to one of ordinary skill in the art at the time of filing to have administered the therapeutic peptide of Lang in combination with memantine and a ChEI according to Atri, for the treatment of a subject having AD and thereby arrive at the presently claimed invention. MPEP § 2144.06, section I, states that “[i]t is prima facie obvious to combine two compositions each of which is taught by the prior art to be useful for the same purpose, in order to form a third composition to be used for the very same purpose.... [T]he idea of combining them flows logically from their having been individually taught in the prior art.” In re Kerkhoven, 626 F.2d 846, 850, 205 USPQ 1069, 1072 (CCPA 1980) (citations omitted). In the instant case, not only are both the therapeutic peptide of Lang and therapeutic agents of Atri (ChEI + memantine) taught to be useful for the treatment of AD, but Lang teaches that the therapeutic peptide can be used in conjunction with a neural growth factor, indicating its suitability for combination with other therapeutic strategies and/or agents. Additionally, Atri teaches that combination of memantine and a ChEI are more effective than monotherapy for inhibiting the cognitive and functional decline in AD patients. Therefore, the combined administration of the prior art agents for the treatment of a subject having AD would have been obvious and predictable.
Conclusion
9. No claims are allowed.
Advisory Information
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/KIMBERLY BALLARD/Primary Examiner, Art Unit 1675